Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was undertaken between 17. October and 6. November 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
All rats were acclimated to the experimental environment for a minimum of 7 days prior to the start of the main study. The rats were randomly allocated to cages within the treatment groups. They were house in groups by sex in metal cages with wire mesh floors. A standard laboratory rodent diet and water were provided ad libitum.
Temperature: 20 - 23 °C
Relative humidtiy: 62%
Air exchange: 15/h
Aritificial light: 12h in each 24 hour period
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
The test substance was administered to each rat using a syringe and plastic catheter
Doses:
1.6 g/kg
2.5 g/kg
3.2 g/kg
4.0 g/kg
No. of animals per sex per dose:
5
Control animals:
no
Preliminary study:
The results of the preliminary studies indicated that the LD 50 of VA-044 was in the region of 2500 mg/kg BW
Sex:
female
Dose descriptor:
LD50
Effect level:
2 800 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
3 200 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 000 mg/kg bw
Based on:
test mat.
Mortality:
Death occurred amongst rats treated at 2.5 g/kg BW and above generally within one and three hours of dosing. One animal treated at 4.0 g/kg was found dead an Day 2.
Clinical signs:
Pilo - erection was observed shortly after dosing in all rats. Abnormal body carriage (hunched posture) also observed in all rats treated at 1.6, 2.5 and 3.2 g/kg and in thre rats treated at 4.0 g/kg bw. These signs were accompaniedby:
abnormal gait (waddling), lethargy, decreased resiratory rate and Palloepf the extremities amomgst rats treated at 2.5 g/kg and above
increased salivation in all rats treated at 3.2 and 4,0 g/kg
prostration in one female rat treated at 2.5 and one male and three female rats treated at 4.0 g/kg
clonic convulsion in one male rat dosed at 4.0 g/kg.
Recovery of survivors, as judged by external appearance and behaviour, was apparently complete by day 3 or 4.
Body weight:
No bodyweight loss or minimal bodyweight losses were recorded for the animals that dies.
Gross pathology:
Renal pallor was observed at autopsy of the rat found dead on Day 2.
Autopsy findings of all other rats that died were normal
Interpretation of results:
GHS criteria not met
Conclusions:
The acute median lethal oral dose (LD50) and their 95 % confidence limits to rats of VA-044 were estimated to be:

Males and females combined: 3000 mg/kg bw
Males only : 3200 mg/kg bw
Females only : 2800 mg/kg bw
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. certificate)
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Standard laboratory conditions. Air-conditioned with 10 - 15 air changes per hour, continuously monitored environmental conditions (temp. range: 22 ± 3 °C;
relative humidity range: 30 - 70 %). On some isolated occasions, the relative humidity in the animal room exceeded the upper limit of 70 %. This is considered to
have no impact on the scientific validity of the study. The light cycle was set to 12-hour fluorescent light / 12-hour dark cycle with at least eight hours music during the light period.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
> 1.89 - < 2.18 µm
Geometric standard deviation (GSD):
> 1.5 - < 3
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
No. of animals per sex per dose:
5
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
> 5.1 mg/L air
Based on:
other: gravimetrically determined mean aerosol concentration
Exp. duration:
4 h
Mortality:
All animals exposed to 2.0 mg/L air survived the scheduled observation period. One female exposed to 5.1 mg/L air was found dead on test day 5. All other animals exposed to 5.1 mg/L air survived the scheduled observation period
Clinical signs:
other: Clinical signs were limited to the day of exposure. All animals of both groups showed slightly ruffled fur after exposure. Two males and four females exposed to 5.1 mg/L air additionally showed salivation during the second half of exposure. The animal whi
Body weight:
Between test days 1 and 2, reduced body weight gain or slight body weight loss was noted in all males exposed to 2.0 or 5.1 mg/L air. This continued in one male exposed to 5.1 mg/L air until test day 8. Thereafter, normal body weight development was noted in all males.
Between test days 1 and 4, reduced body weight gain or slight body weight loss was noted in all females exposed to 2.0 or 5.1 mg/L air. This continued in to females exposed to 2.0 mg/L air until test day 8 and in another two females exposed to 2.0 mg/L air until test day 15.
Other findings:
Macroscopic Findings
No test item-related macroscopic findings were present at necropsy. All findings observed were within the range of spontaneous background lesions which may occasionally be recorded in rats of this strain and age.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the findings of this study, the LC50 for 4-hour exposure of Azo Initiator VA044 was greater than 5.1 mg/L air (gravimetrically determined mean aerosol concentration). Based on mortality and body weight data, females are considered to be more susceptible to the toxicity of the test item.
Executive summary:

Treatment of RccHanTM:WIST(SPF) rats with Azo Initiator VA044 at gravimetrically determined mean concnentrations of 2.0 mg/L air and 5.1 mg/L air for 4 hours did not result in any deaths at 2.0 mg/L air. One female died on test day 5 after exposure to 5.1 mg/L air. Clinical signs of toxicity were limited to the day of exposure and no test item-related macroscopic findings were observed. Between test days 1 and 2, reduced body weight gain or slight body weight loss was noted in all males exposed to 2.0 or 5.1 mg/L air. This continued in one male exposed to 5.1 mg/L air until test day 8. Thereafter, normal body weight development was noted in all males. Between test days 1 and 4, reduced body weight gain or slight body weight loss was noted in all females exposed to 2.0 or 5.1 mg/L air. This continued in to females exposed to 2.0 mg/L air until test day 8 and in another two females exposed to 2.0 mg/L air until test day 15. Although body weight loss or stagnation of body weight gain is not unusual in inhalation studies due to the restraining of the animals in the tubes during nose-only exposure, the effect in females exposed to 2.0 mg/L air and in both sexes exposed to 5.1 mg/L air is considered to be test itemrelated due to the magnitude and duration of body weight loss observed. Based on the findings of this study, the LC50 for 4-hour exposure of Azo Initiator VA044 was greater than 5.1 mg/L air (gravimetrically determined mean aerosol concentration). Based on mortality and body weight data, females are considered to be more susceptible to the toxicity of the test item.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 100 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

In both available acute toxicity studies no adverse effect is observed at the highest test concentration. Due to these findings it is concluded that the substance does not fulfil the criteria for classification as acute toxic.